AB0407 EFFICACY AND SAFETY OF 144-WEEK TREATMENT WITH TACROLIMUS AS THE FIRST-LINE CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUG (csDMARD) FOR PATIENTS WITH ACTIVE REFRACTORY RHEUMATOID ARTHRITIS： A PROSPECTIVE, COHORT STUDY
Authors: Y. Li, F. Wang, Y. Sui, J. Chen, T. Zhang, Q. Shu
Journal: Annals of the Rheumatic Diseases (2022)

Background The T2T guideline in RA recommended the normal csDMARDs irresponsive patients (pts) switching to other treatment target. Tacrolimus (TAC), the inhibitor of T cell activation, is candidate for these pts, especially with extrarticular complications (EC). Objectives To observe the efficacy and safety of TAC-based csDMARDS regimen refractory RA (RRA) pts and the characteristics of TAC combined treatment. Methods This prospective cohort study (ClinicalTrials.gov Identifier NCT02837978 ) was conducted in China. According to baseline DAS28-ESR, RRA pts (ACR 1987 criteria [1]) were classified to severe (&gt;5.1, S) or moderate (&gt; 3.2,≦5.1, M) groups. The efficacy indicators and AE were recorded untill 144w. The combined medicine with TAC was based on the past history of csDMARD prescription and EC, including TAC with/wo MTX (T+M or T group), Pred, HCQ. Results 150 pts (52±14y) were involved, 15 finished 144w observation, 50 still following up and 85 lost. As shown with GEE analysis, DAS28-ESR, CRP, HAQ were decreased significantly in all pts within 24ws, and maintained stable in later period (Figure 1). The REM or LDA, achieved ACR20, good or moderate EULAR response (G+M) proportion of 103 pts completed the 24w were 41.75%, 56.31%, 76.70%. Figure 1. Disease activity index of 150 RRA pts decreased in 144weeks Similar to the Japanese study [2], DAS28-ESR, CRP and HAQ typically declined rapidly in S group, but still higher than M (Figure 2A-C). According to GBTM analysis, S group, longer disease course or higher HAQ had a higher ACR20 remission rate (Figure 2D). Figure 2. Disease activity index of 103 pts declined rapidly in 24weeks. (A ). DAS28-ESR; (B ) CRP; (C ). HAQ declined significantly in S (n=53) than M (n=50) during 24ws. (D ).higher increased ACR20 remission group (90.6%), compared with low-stable (0%) in 24ws. * p &lt; 0.05, compared to M; # p &lt; 0.05, compared to baseline. A total of 69 RA pts (46.0%) had 177 times (23.07%) AE, including 2 SAEs. Infection was the dominating AE (30%) due to asymptomatic positive urinary leucocyte and cold were classified, higher than (3.4%) Japanese study [3]. AEs were mainly happened in pts with higher TAC blood concentration 4.55(3-14.5) ng/ml, compared to No AE group 3.8(2.4-7.8) ng/ml, p =0.048, extremely in those abnormal glucose tolerance and hypertensive pts, p =0.002, 0.022. The most common reasons of lost were drug ineffective (32.94%), economic reasons (29.1%). There was no difference in efficacy of TAC combined treatment. Combination MTX reduce AE, decrease the usage rate and dosage of Pred. Combination Pred increased AE. Pts that achieved REM+LDA, G+M, had better TAC survival rate (Figure 3A-B). The combination of MTX, HCQ reduce lost rate (Figure 3C-D). Figure 3. TAC survival ratio were compared in different response and csDMARDs combination groups. (A ).The pts acquired remission (n= 31) or LDA (n= 18) had higher TAC survival rate than high (n=28) &amp; moderate (n=73) group, * p &lt; 0.05, compared to group High; # p &lt; 0.05, compared to Moderate; &amp; p &lt; 0.05, compared to Low; (B ). The pts G+M (n=95) had better TAC survival rate, compared with no response (N, n=55), ** p &lt; 0.01; (C ). Combine MTX reduced lost rate, ** p &lt; 0.01, compared to T; (D ). Combine MTX and HCQ reduced lost rate, * p &lt; 0.05 compared to MTX-HCQ-; # p &lt; 0.05 compared to MTX+HCQ-. The Logistic regression showed baseline DAS28-ESR was an independent protective factor for poor response. Baseline DAS28-ESR and previous Perd use were independent protective factors for ACR20 remission. Conclusion TAC-based combined therapies are effective and tolerable for RRA, especially to the higher disease activity pts. TAC blood concentration related to AE. The lower disease activity index and better respond, the higher TAC survival ratio. MTX is recommended as TAC combined treatment. References [1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281. [2]Kanzaki T,et al., Rheumatology International,2013. 33(4):871-877. [3]Takeuchi T, et al. Mod Rheumatology 2018,28(1): 48-57. Acknowledgements Acknowledgements: Funded by ECCM Program of Clinical Research Center of Shandong University (No. 2021SDUCRCB010) Disclosure of Interests None declared